U.S. 20140044828 describes nutritional compositions containing specified amounts of n-3 fatty acids and one or more of free lysine, dipeptides containing lysine, and lysine salts, for the prophylaxis and/or treatment of various symptoms associated with muscle mass decrease, decreased basal metabolism, and low body temperature, as well as for suppression of obesity, suppression of visceral fat accumulation, and treatment of hyperglycemia and hyperlipidemia, particularly in the elderly. The term “dipeptides containing lysine” is defined as referring to a dipeptide where at least one molecule of the dipeptide is lysine or a salt of lysine such as L-lysine hydrochloride, L-lysine acetate, and L-lysine glutamate. Lysyllysine is given as a specific example of a dipeptide containing lysine.
Lysyllysine is described in U.S. 20080248564 in a process for the covalent modification of nucleic acids by lactosylation for more efficient transfer of nucleic acids into cells. This is described as an improvement over prior art methods relying on the formation of non-specific ionic complexes between nucleic acids and polycations such as polylysine, as described in U.S. Pat. No. 5,166,320. U.S. 20060084617 describes the use of lysyllysine in a process for conjugating endosomolytic spermine to nucleic acids to enhance their delivery into cells.
U.S. 20070275019 describes the preparation of vaccines directed to cancer-associated carbohydrate antigens, the vaccines comprising multivalent antigen systems in which lysyllysine is used as a core matrix bearing multiple antigens as dendritic arms
Polyunsaturated fatty acids of the omega-3 series (“omega-3 fatty acids”) have shown a wide spectrum of biological activities suggesting their possible usefulness in treating a range of diseases and disorders including metabolic disorders, cardiovascular complications, inflammatory diseases, central nervous system disorders, and ophthalmic complications. But the poor aqueous solubility of omega-3 fatty acids limits their utility as therapeutic agents and as nutraceutical additives to food and drink due to a phenomenon referred to as solubility-limited absorption which limits the plasma levels that can be achieved following oral administration. In fact, the omega-3 fatty acids are essentially insoluble in water and both the free acid and sodium salt forms create soap-like emulsions when mixed with water. Thus, although omega-3 fatty acids are absorbed following oral administration, the relatively low plasma levels achieved cannot be increased simply by increasing the dose administered.
WO 2014/011895 describes fatty acid salts of eicosapentaenoic acid (EPA) with lysine or docosahexaenoic acid (DHA) or EPA with metformin, piperazine, and meglumine. The compositions provide for increased aqueous solubility of the fatty acid.
In addition to their poor aqueous solubility, omega-3 fatty acids suffer from susceptibility to lipid oxidation. This oxidation leads to formation of undesirable fishy and rancid off-flavors that render compositions comprising them less palatable.
There is a need to develop compositions able to deliver omega-3 fatty acids at much higher plasma levels than is possible using the currently available free fatty acid, sodium salt, or ester forms, in order to fulfill the therapeutic promise of these compounds and translate the many promising in vitro and cellular pharmacology observations into clinical benefits. Such compositions should demonstrate increased aqueous solubility of omeg-3 fatty acids which would facilitate their use in both oral dosage forms, ophthalmic drops, and intravenous dosage forms. There is also a need to develop compositions that provide improved stability of the omega-3 fatty acids against lipid oxidation. The present invention addresses these needs.